Publications (14)237.34 Total impact
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Article: Moderate alcohol consumption is associated with reduced long-term cardiovascular risk in patients following a complicated acute myocardial infarction.
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ABSTRACT: The impact on prognosis of alcohol use in patients with coronary artery disease remains uncertain. We related alcohol use to all-cause mortality, cardiovascular (CV)-mortality and hospitalization in patients following a complicated myocardial infarction (MI). In the OPTIMAAL trial, 5477 patients from 7 Western European countries with heart failure and/or evidence of left ventricular dysfunction following MI were recruited. Following randomization median 3 days, patients were asked to assess their average alcohol consumption prior to the index infarction. Patients were stratified by the frequency of the use of alcohol into either non-users (n = 2160), moderate users (1-7 drinks/week, n = 2753) and heavy users (> 7 drinks/week, n = 545) and related to prespecified clinical outcomes in the groups. A total of 5477 patients were included in the trial. During the follow-up period of 2.7 years 946 deaths were reported. Adjusted for age and smoking status, patients with moderate use of alcohol had 24% lower risk of all-cause death (p < 0.001), 26% lower risk of CV-death (p < 0.000) and 8% lower risk for hospitalization (p = 0.030) than abstainers. There was no significant difference between non-drinkers and heavy drinkers with regard to survival following adjustment for age and smoking status. Our results demonstrate a strong positive association between moderate alcohol use and survival in a cohort of patients following complicated MI. Both heavy drinkers and abstainers had poorer prognosis, with no significance difference between those 2 groups.International journal of cardiology 03/2008; 133(2):229-32. · 7.08 Impact Factor -
Article: The impact of morbid events on survival following hospitalization for complicated myocardial infarction.
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ABSTRACT: Little is known about the importance of morbid events with respect to longer term survival following MI hospital discharge. Establish the risk of death associated with morbid events following initial discharge from MI hospitalization. We examined the rates of morbid events (reinfarction, stroke/TIA, revascularization, heart failure (HF) hospitalization, cardiovascular hospitalization and all-cause hospitalization) and the relationships of these events to subsequent death in patients who survived the initial hospitalization for MI (n = 5301) in the OPTIMAAL trial. Events were classified as Early (< or = 30 days post discharge) and Late (> 30 days post discharge) for an average of 2.7 years follow-up. Death rates were higher in the Early period (0.20 deaths/patient year) than in the Late period (0.05 deaths/patient year). Once a morbid event, excluding revascularization, occurred, the acute hazard ratios (HR, determined by Cox regression) for death on the day of event were higher than at time periods following the event and were highest for reinfarction and stroke/TIA. The acute HRs for death for all 6 morbid events were especially high for events occurring during the Late period. The highest chronic HR for death was associated with HF and all-cause hospitalizations. By contrast, the chronic HR for death from revascularization in both the Early (HR = 0.3) and Late (HR = 0.4) period indicated reduced risk. The results document event rates following hospitalization for MI, provide quantification of the associated risk for death, and may be useful in designing clinical trials. The serious morbid events examined may serve as potential surrogate endpoints in long-term studies and identify patients that should be targeted for aggressive management.European Journal of Heart Failure 02/2006; 8(1):74-80. · 4.90 Impact Factor -
Article: Prognostic risk of atrial fibrillation in acute myocardial infarction complicated by left ventricular dysfunction: the OPTIMAAL experience.
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ABSTRACT: The present study aimed to determine the frequency and the impact on clinical outcome of atrial fibrillation (AF) in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. In the OPTIMAAL trial, 5477 patients with AMI and signs of left ventricular dysfunction were included. At baseline, 655 patients (12%) had AF, and 345 (7.2%) developed new-onset AF during follow-up (2.7 +/- 0.9 years). Older patients, patients with history of angina and worse Killip class had and developed AF more frequently (P < 0.001). Patients with AF at baseline were at increased risk relative to those without AF for mortality [adjusted hazard ratio (HR) of 1.32, P = 0.001] and for stroke (HR 1.77, P < 0.001). New-onset AF was associated with increased subsequent mortality for the first 30 days following randomization (HR 3.83, P < 0.001) and the entire trial period (HR 1.82, P < 0.001). Risk of stroke was increased for the first 30 days (HR 14.6, P < 0.001) and for the whole trial period (HR 2.29, P < 0.001). AF is frequently observed in patients with AMI complicated by heart failure. Current AF, and the development of new AF soon after AMI, is associated with increased risk of death and stroke.European Heart Journal 02/2005; 26(4):350-6. · 10.48 Impact Factor -
Article: Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events.
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ABSTRACT: Electrocardiographic left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular (CV) morbidity and mortality. However, the predictive value of changes in the magnitude of electrocardiographic LVH criteria during antihypertensive therapy remains unclear. To test the hypothesis that lesser severity of electrocardiographic LVH during antihypertensive treatment is associated with decreased CV morbidity and mortality, independent of blood pressure levels and reduction and treatment modality. Double-blind, randomized, parallel-group study conducted in 1995-2001 among 9193 men and women with hypertension aged 55 through 80 years (mean, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage criteria and enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. Losartan- or atenolol-based treatment regimens, with follow-up assessments for at least 4 (mean, 4.8 [SD, 0.9]) years. Composite end point of CV death, myocardial infarction (MI), or stroke in relation to severity of electrocardiographic LVH determined at baseline and on subsequent electrocardiograms obtained at 1 or more annual revisits. Cardiovascular death, nonfatal MI, or stroke occurred in 1096 patients (11.9%). In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline and in-treatment blood pressure, and severity of baseline electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage, less-severe in-treatment LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point (adjusted hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.82-0.90; P<.001 for every 1050-mm x ms [1-SD] decrease in Cornell product; and HR, 0.83; 95% CI, 0.78-0.88; P<.001 for every 10.5-mm [1-SD] decrease in Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P<.001; and HR, 0.80; 95% CI, 0.73-0.87; P<.001, respectively), MI (HR, 0.90; 95% CI, 0.82-0.98; P=.01; and HR, 0.90; 95% CI, 0.81-1.00; P = .04), and stroke (HR, 0.90; 95% CI, 0.84-0.96; P=.002; and HR, 0.81; 95% CI, 0.75-0.89; P<.001). Less-severe electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, independent of blood pressure lowering and treatment modality in persons with essential hypertension. Antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may improve prognosis.JAMA The Journal of the American Medical Association 11/2004; 292(19):2343-9. · 30.03 Impact Factor -
Article: Electrocardiographic strain pattern and prediction of cardiovascular morbidity and mortality in hypertensive patients.
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ABSTRACT: The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.Hypertension 08/2004; 44(1):48-54. · 6.21 Impact Factor -
Article: Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure.
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ABSTRACT: This retrospective, nonrandomized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infarction compared with the effect of neither or both treatments. Early initiation of statins or beta blockers alone was associated with improved event-free survival, and the benefits of the combined treatment were additive.The American Journal of Cardiology 04/2004; 93(5):603-6. · 3.37 Impact Factor -
Article: Effect of losartan on sudden cardiac death in people with diabetes: data from the LIFE study.
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ABSTRACT: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a major reduction of all-cause mortality--especially cardiovascular mortality--in patients with diabetes with left ventricular hypertrophy was reported for treatment with losartan. We postulated post hoc that losartan might have a better effect on sudden cardiac death than atenolol, and we aimed to test this hypothesis. 44 patients with diabetes died of sudden cardiac death; significantly fewer deaths arose in the losartan group (14) than in the atenolol group (30; p=0.027). In the losartan group, five (6%) of 86 patients with diabetes and atrial fibrillation during the trial died of sudden cardiac death compared with nine (2%) of 500 in those without atrial fibrillation. The respective figures for the atenolol group were 14 (13%) of 105 and 16 (3%) of 504. Our results suggest losartan affords better protection against cardiac death from arrhythmias for patients with diabetes mellitus than does atenolol. Importantly, our analyses were exploratory and require confirmation.The Lancet 09/2003; 362(9384):619-20. · 38.28 Impact Factor -
Article: Effects of losartan or atenolol in hypertensive patients without clinically evident vascular disease: a substudy of the LIFE randomized trial.
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ABSTRACT: Cardiovascular morbidity and mortality are reduced by treatment with the angiotensin II AT(1)-receptor antagonist losartan compared with conventional treatment with the beta-blocker atenolol in patients with hypertension and electrocardiogram-defined left ventricular hypertrophy, many of whom had known vascular disease. To determine whether losartan reduces cardiovascular event rates in lower-risk hypertensive patients without clinically evident vascular disease. Subgroup analysis of a randomized trial. The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. 6886 men and women (57% women) 55 to 80 years of age (average, 66 years) with essential hypertension (sitting blood pressure, 160 to 200/95 to 115 mm Hg [average, 174/98 mm Hg]) and electrocardiogram-defined left ventricular hypertrophy who did not have clinically evident vascular disease. Patients were randomly assigned to once-daily double-blind treatment with losartan or atenolol. An end point committee ascertained end points (cardiovascular death, stroke, or myocardial infarction). Blood pressure was reduced similarly by losartan and atenolol. The primary composite end point occurred in 282 losartan-treated patients (17.5 per 1000 patient-years) and 355 atenolol-treated patients (21.8 per 1000 patient-years; relative risk, 0.81 [95% CI, 0.69 to 0.95]; P = 0.008). Cardiovascular death occurred in 103 losartan-treated patients and 132 atenolol-treated patients (relative risk, 0.80 [CI, 0.62 to 1.04]; P = 0.092), stroke (nonfatal and fatal) occurred in 125 losartan-treated patients and 193 atenolol-treated patients (relative risk, 0.66 [CI, 0.53 to 0.82]; P < 0.001), and myocardial infarction (nonfatal and fatal) occurred in 110 losartan-treated patients and 100 atenolol-treated patients (relative risk, 1.14 [CI, 0.87 to 1.49]; P > 0.2). New-onset diabetes occurred less often in patients treated with losartan (n = 173) than in patients treated with atenolol (n = 254) (relative risk, 0.69 [CI, 0.57 to 0.84]; P < 0.001). Benefits of losartan treatment were numerically smaller, but not significantly so, in patients with preexisting vascular disease. In hypertensive patients without clinically evident vascular disease, losartan was more effective than atenolol in preventing cardiovascular morbidity and death, predominantly stroke, independent of blood pressure reduction.Annals of internal medicine 09/2003; 139(3):169-77. · 16.73 Impact Factor -
Article: Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study.
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ABSTRACT: Electrocardiographic left ventricular hypertrophy (LVH) predicts cardiovascular morbidity and mortality, and regression of ECG LVH may predict improved prognosis in hypertensive patients. However, uncertainty persists as to how best to regress ECG LVH. Regression of ECG LVH with losartan versus atenolol therapy was assessed in 9193 hypertensive patients with ECG LVH by Sokolow-Lyon voltage or Cornell voltage-duration product criteria enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Patients had ECGs at study baseline and after 6 months, 1, 2, 3, 4, and 5 years of blinded losartan-based or atenolol-based therapy. After 6 months' follow-up, adjusting for baseline ECG LVH levels, baseline and in-treatment systolic and diastolic pressures, and for diuretic therapy, losartan-based therapy was associated with greater regression of both Cornell product (adjusted means, -200 versus -69 mm. ms, P<0.001) and Sokolow-Lyon voltage (-2.5 versus -0.7 mm, P<0.001) than was atenolol-based therapy. Greater regression of ECG LVH persisted at each subsequent annual evaluation in the losartan-treated group, with between 140 and 164 mm. ms greater mean reductions in Cornell product and from 1.7 to 2.2 mm greater mean reductions in Sokolow-Lyon voltage (all P<0.001). The effect of losartan was consistent across subgroups defined by gender, age, ethnicity, and diabetes. After adjusting for baseline and in-treatment blood pressure and baseline severity of ECG LVH, losartan-based antihypertensive therapy resulted in greater regression of ECG LVH by Cornell voltage-duration product and Sokolow-Lyon voltage criteria than did atenolol-based therapy. These findings support the value of angiotensin receptor blockade with losartan for reversing ECG LVH.Circulation 08/2003; 108(6):684-90. · 14.74 Impact Factor -
Article: OR-27: The interaction between aspirin and losartan on cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy. A losartan intervention for endpoint reduction (LIFE) substudy
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ABSTRACT: Am J Hypertens (2003) 16, 11A–12A; doi:10.1016/S0895-7061(03)00111-0 OR-27: The interaction between aspirin and losartan on cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy. A losartan intervention for endpoint reduction (LIFE) substudy Eigil Fossum1, Sverre E. Kjeldsen1, Björn Dahlöf1, Richard B. Devereux1, Stevo Julius1 and Steven Snapinn11Department of Cardiology, Ullevaal University Hospital, Oslo, Norway; Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden; Division of Cardiology, Cornell Medical Center, New York; Department of Internal Medicine, Division of Hypertension, University of Michigan, Ann Arbor; Merck & Co. Inc., Whitehouse Station, NJ USAAmerican Journal of Hypertension 04/2003; · 3.18 Impact Factor -
Article: Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study.
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ABSTRACT: There has been uncertainty about the risk of new-onset diabetes in hypertensive individuals treated with different blood pressure-decreasing drugs. To study this risk in hypertensive individuals who were at risk of developing diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. In the LIFE study, with a double-masked, randomized, parallel-group design, 9193 patients (46% men) with hypertension (mean age 67 years, average pressure 174/98 mmHg after placebo run-in) and electrocardiogram-documented left ventricular hypertrophy were randomly assigned to once-daily losartan- or atenolol-based antihypertensive treatment and followed for at least 4 years (mean 4.8 years). At baseline, 7998 patients did not have diabetes mellitus and were thus at risk of developing this condition during the study. To demonstrate ability to predict new-onset diabetes, we developed a prediction score using the significant variables from multivariate analyses (serum glucose, body mass index, serum high-density lipoprotein cholesterol, systolic blood pressure and history of prior use of antihypertensive drugs). There was a steadily increasing risk of diabetes with increasing level-of-risk score; patients in the highest quartile were at considerably greater risk than those in the three lower ones. Treatment with losartan was associated with lower risk of development of diabetes within each of the four quartiles of the risk score. As previously reported, new-onset diabetes mellitus occurred in 242 patients receiving losartan (13.0 per 1000 person-years) and 320 receiving atenolol (17.5 per 1000 person-years); relative risk 0.75 (95% confidence interval 0.63 to 0.88; P<0.001). New-onset diabetes could be strongly predicted by a newly developed risk score using baseline serum glucose concentration (non-fasting), body mass index, serum high-density lipoprotein cholesterol concentration, systolic blood pressure and history of prior use of antihypertensive drugs. Independently of these risk factors, fewer hypertensive patients with left ventricular hypertrophy developed diabetes mellitus if they were treated with losartan than if they were treated with atenolol.Journal of Hypertension 10/2002; 20(9):1879-86. · 4.02 Impact Factor -
Article: Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy.
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ABSTRACT: Drug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension. To test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH). Double-blind, randomized, parallel-group study conducted in 1995-2001. A total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States. Patients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years. Composite end point of cardiovascular death, stroke, or myocardial infarction. Blood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; 95% confidence interval [CI], 0.56-1.01; P =.06, adjusted for risk and degree of ECG-LVH; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P =.02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P =.01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P =.02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P =.04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P =.046). Losartan decreased ECG-LVH more than atenolol (P<.001) and was better tolerated. These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.JAMA The Journal of the American Medical Association 09/2002; 288(12):1491-8. · 30.03 Impact Factor -
Article: Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.
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ABSTRACT: The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients. As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction). Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002. Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.The Lancet 04/2002; 359(9311):1004-10. · 38.28 Impact Factor -
Article: Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients With Isolated Systolic Hypertension and Left Ventricular HypertrophyA Losartan Intervention For Endpoint Reduction (LIFE) Substudy
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ABSTRACT: Context Drug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension.Objective To test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH).Design Double-blind, randomized, parallel-group study conducted in 1995-2001.Setting and Participants A total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States.Interventions Patients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years.Main Outcome Measure Composite end point of cardiovascular death, stroke, or myocardial infarction.Results Blood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; 95% confidence interval [CI], 0.56-1.01; P = .06, adjusted for risk and degree of ECG-LVH; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P = .02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P = .01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P = .02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P = .04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P = .046). Losartan decreased ECG-LVH more than atenolol (P<.001) and was better tolerated.Conclusion These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH. Figures in this Article As described previously,1 the Losartan Intervention For Endpoint reduction (LIFE) study was designed in the early 1990s when (1) reduction of cardiovascular (CV) morbidity and mortality with β-blocker- or diuretic-based antihypertensive therapy was suboptimal,2- 5 (2) left ventricular hypertrophy (LVH) was a cardinal manifestation of preclinical CV disease and was a strong and independent risk factor for CV complications in hypertension, (3) indications that reversal of LVH was thought to have had prognostic benefit independent of blood pressure,6- 7 (4) there was an association of angiotensin II with development of LVH, and (5) suggestive evidence that blocking angiotensin II was thought to be especially effective in reversing LVH and could confer protective benefits over and above blood pressure lowering.8 Losartan was the first available selective AT1-receptor antagonist.9 Atenolol was chosen as a comparative agent to losartan in the LIFE study1 because it has similar antihypertensive effectiveness as losartan10 and because β-blockers have been recognized as a first-line therapy for cardiovascular protection in hypertension.11- 12 Isolated systolic hypertension (ISH) carries higher risk than isolated diastolic blood pressure elevation.13- 14 The outcome of drug intervention in placebo-controlled trials has been highly beneficial in patients with ISH.15- 17 In a predefined substudy of LIFE,18 we tested the hypothesis that losartan has preventive effects beyond blood pressure control in patients with ISH and LVH. This is the first comparative drug trial to report CV outcomes in ISH.JAMA The Journal of the American Medical Association 288(12):1491-1498. · 30.03 Impact Factor
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2003
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Sahlgrenska University Hospital
Göteborg, Vaestra Goetaland, Sweden
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2002
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Umeå University
Umeå, Vaesterbotten, Sweden -
Steno Diabetes Center
Gentofte, Capital Region, Denmark
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